Crizotinib with Atazanavir Interaction Details
Brand Names Associated with Crizotinib
- Crizotinib
- Xalkori®
Brand Names Associated with Atazanavir
- Atazanavir
- ATZ
- Reyataz®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 29, 2024
Interaction Effect
Increased crizotinib exposure, increased atazanavir exposure and an increased risk of QT interval prolongation
Interaction Summary
Coadministration of atazanavir with crizotinib is contraindicated. Atazanavir is a strong CYP3A4 inhibitor[1], crizotinib is a moderate CYP3A4 inhibitor [2], and both drugs are CYP3A4 substrates associated with QT-interval prolongation. Concurrent use may lead to an increased risk of serious cardiac adverse events, including torsade de pointes [2][1]. Although this specific interaction has not been studied, atazanavir is contraindicated for coadministration with drugs highly dependent on CYP3A for clearance and for which elevated plasma levels may result in serious or life-threatening events, such as crizotinib [1]; additionally, concurrent use of atazanavir with crizotinib may increase exposure of atazanavir [2].
Severity
Contraindicated
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of atazanavir with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma levels may result in serious or life-threatening events, such as crizotinib, is contraindicated[1]. Concurrent use of crizotinib, a moderate CYP3A4 inhibitor, with a drug that is predominantly metabolized by CYP3A4, such as atazanavir, may result in increased atazanavir exposure [2]. Additionally, both atazanavir and crizotinib are known to prolong the QT interval and concurrent use of these agents may lead to an increased risk of serious cardiac adverse events, including torsade de pointes [1][2].
Mechanism Of Interaction
Inhibition of CYP3A-mediated crizotinib metabolism by atazanavir; inhibition of CYP3A-mediated atazanavir metabolism by crizotinib; additive QT interval prolongation
Literature Reports
A) In a pharmacokinetic study, coadministration of crizotinib (250 mg twice daily for 28 days) with oral midazolam resulted in a 3.7-fold increase in the geometric mean midazolam AUC compared with midazolam administered alone. This clinical study with a CYP3A4 substrate suggests that crizotinib is a moderate inhibitor of CYP3A4 [2].
B) In a drug interaction study of crizotinib and ketoconazole (a strong CYP3A4 inhibitor), concomitant use of a single 150-mg dose of crizotinib with ketoconazole 200 mg twice daily increased crizotinib AUC and Cmax by approximately 3.2-fold and 1.4-fold, respectively, compared with crizotinib exposure when given alone [2].
References
1 ) Product Information: REYATAZ(R) oral capsules, atazanavir sulfate oral capsules. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2013.
2 ) Product Information: XALKORI(R) oral pellets, oral capsules, crizotinib oral pellets, oral capsules. Pfizer Labs (per FDA), New York, NY, 2023.
Crizotinib Overview
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Crizotinib is used to treat certain types of non-small cell lung cancer (NSCLC) that has spread to nearby tissues or to other parts of the body. It is also used to treat a certain type of anaplastic large cell lymphoma (ALCL) that has returned or is unresponsive to other treatment(s) in certain adults and children 1 year of age and older. Crizotinib is also used to treat a certain type of inflammatory myofibroblastic tumor (IMT; type of cancer that occurs in mucosal tissues usually in the abdominal area, involving the lungs, bladder, stomach, uterus, liver, or intestines) that cannot be treated with surgery or that has not improved or has come back after previous treatment(s) in adults and children 1 year of age and older. Crizotinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply.
Atazanavir Overview
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Atazanavir is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children who are at least 3 months of age and weigh at least 22 lb (10 kg). Atazanavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although atazanavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Atazanavir must be given with other medications that treat HIV infection to completely treat the infection. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.